Research Resources Much of this research is based on three large epidemiologic observational cohorts the AGES- Reykjavik Study (Age Gene/Environment Susceptibility-Reykjavik Study), and the HAAS (Honolulu Asia Aging Study), and The Coronary Artery Risk Development in Young Adults Study (CARDIA). CARDIA began in 1985-6 with a group of 5115 black and white men and women aged 18-30 years. AGES-RS includes men and women born 1907-1935 and the HAAS includes Japanese American men born 1900-1919. Both AGES-RS and HAAS cohorts were established in the mid-1960s to answer questions about the heart disease epidemic that became a public health priority during that decade. All studies have similar measures of cardiovascular risk factors in middle-age, which is invaluable when trying to understand epidemiologic studies designed to investigate etiology. Since the mid-life data are similar, and both studies identify dementia cases, this provides an excellent opportunity to replicate findings from one cohort, in the other cohort. The studies also have complementary measures of brain aging; whereas the HAAS includes a rich autopsy sub-study, AGES- Reykjavik has a wealth of cognitive, MRI and clinical data, while CARDIA has state-of-the-art measures on brain MRI. HAAS The Honolulu-Asia Aging Study (HAAS) began in 1991 as a continuation of the Honolulu Heart program (HHP), a population-based longitudinal study of Japanese-American men born between 1900 and 1919 and living in Oahu, Hawaii when the study began in 1965. Participants were seen at three mid-life exams (1965-68, 1968-70, 1971-74), and at four exams in late-life (1991-93, 1994-96, 1997-99; 2001-02). Clinical measurements, demographic, and medical information were collected at each exam. Starting in 1991, global cognitive function was measured in the total sample and cases of dementia ascertained. An autopsy study nested within the cohort was also started in 1991; to date over 600 men have come to autopsy. A MRI sub-study of 575 men was performed in 1995-1996. Active data collection has ended, after 20 years. Data will continue to be analyzed. This study has made several major advances in the field including: risk factors in mid-life modulate risk for late-life dementia; risk factors change over time with developing dementia; people have multiple types of neurodegenerative and vascular lesions in the brain and they contribute to ante-mortem cognition; micro-infarcts are a prevalent neuropathologic lesion that contribute to dementia. AGES- Reykjavik is a population-based follow up study of men and women born 1907-1934. The cohort was established in 1967 by the Icelandic Heart Association; participants were followed up to six times. To advance our understanding of genetic and non-genetic risk factors, AGES- Reykjavik focuses on obtaining high quality quantitative measures of intermediate components of major diseases of old age. To this end, extensive bio-image and bio-specimen phenotype measures have been made of multiple physiological systems, including neurocognitive, vascular, musculoskeletal, and body composition, and metabolic measures. This study has made important contributions to understanding the role of small vessel disease as both a consequence of cardiovascular risk factors and a substrate for cognitive impairment, dementia and depression. Work on the heart-brain and kidney-brain axes is in progress, as is continued research on the hemodynamic contribution to brain pathology. CARDIA. The CARDIA Study is a prospective, epidemiologic investigation of the determinants and evolution of cardiovascular risk factors among 5,115 African American and white young adults 18-30 years of age at baseline in 1985-86. Participants were recruited from the populations of four geographic locations (Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA). The CARDIA Coordinating Center is also located at the University of Alabama-Birmingham. The study population was approximately balanced according to sex (54% women), ethnicity (52% African American), and education (40% with less than equal to 12 years of education) at each center. After the 1984 baseline, 7 additional examinations were undertaken. In 2010 the CARDIA Brain MRI study was added to the 25-year follow-up exam. For the first time a novel, detailed investigation of the earliest physiologic and morphologic phases of brain disease process has been conducted in a community-based middle age cohort. This information will prove critical in prevention and early management of CVD, before irreversible damage and functional consequences occurs. We have found that even in a middle age cohort, total brain volume, white matter lesion load, white matter tissue integrity and cerebral blood flow are associated with one or more cardiovascular risk factors, including elevated blood pressure, diabetes, smoking, and sedentary behavior, and that these risk factors lead to measurably lower scores on cognitive function tests. The cohort re-examination in 2016-2017, included a repeat MRI. Data are currently being processed.